We have begun analyzing the factors influencing the regulation of the MHC class II-specific CTL repertoire in vivo. We have used a neonatal injection protocol to study the requirements for induction of antigen-specific tolerance to nonself class II determinants. Our initial experiments have demonstrated that class II allospecific CTL can be effectively tolerized by our protocol and represents (to our knowledge) the first successful to tolerization of this T cell population. We can now compare and contrast the recognition and signalling requirements of L3T4+ and Lyt2+ class II-specific immature CTL populations during neonatal tolerance induction, and relate those findings to what we have already established regarding the recognition and signalling requirements for activation of mature class II-specific CTL populations.